In view of the increased formation of cyclic AMP and catecholamines with neuronal depolarization of brain tissues and our findings that cyclic AMP produces an activation of soluble tyrosine hydroxylase prepared from rat-brain, the objective of this research is to establish that cyclic AMP is involved in the regulation of the rate of catecholamine synthesis. Thus, these studies will investigate the physiological significance of cyclic AMP as an activator of tyrosine hydroxylase, the rate-limiting enzyme of catecholamine biosynthesis, during periods of increased impulse activity. Alterations of neuronal activity will be produced by either stimulating tissue slices electrically or with depolarizing agents or by interrupting discrete anatomical pathways of the rat-brain. The effects of these altered conditions on the rates of conversion of C14-ATP to cyclic AMP and of H3-tyrosine to Dopa and the kinetic properties of adenylate cyclase and tyrosine hydroxylase will be investigated in either brain slices or "broken cell" hypotonic homogenates in order to determine whether cyclic AMP may be partly responsible for the stimulation of tyrosine hydroxylase activity during neuronal depolarization. Results obtained from these studies should contribute significantly to an understanding of the functional relationship existing between the rates of cyclic AMP production and catecholamine synthesis and to our knowledge of whether cyclic AMP produced during neuronal stimulation acts as an activator of tyrosine hydroxylase. Finally, the possibility that the mechanism underlying this effect may involve an activation of a cyclic AMP-dependent protein kinase and subsequent phosphorylation of tyrosine hydroxylase or some activator of this enzyme, will also be investigated.